The mas oncogene has recently been shown to encode an angiotensin receptor which responds preferentially to angiotensins III and II over angiotensin I, and is found primarily in neural tissue. The aim of this proposal is to study the cellular mechanisms which mediate this response and the tumorigenic capacity of the mas gene product in normal tissue. Several approaches will be used. First, the cellular response of a sensory neuron-like cell line (NG115-401L C3) to acute and chronic application of angiotensins will be studied; this clonal cell line has been stably transfected with the mas gene. Second, the effects of point mutations in the mas gene on receptor function will be studied using the Xenopus oocyte expression system. Third, the tissue specificity and timing of expression and tumor formation will be addressed by creating transgenic mice. These studies will be done as a collaborative effort between the principal investigator, Drs. M.R. Hanley, M. Goedert and T.R. Jackson (Medical Research Council, Cambridge, England), and Drs. R. Duvoisin and S. Heinemann (Salk Institute, San Diego).